Interactions of designer antibiotics and the bacterial ribosomal aminoacyl-tRNA site

James B. Murray, Samy Meroueh, Rupert J M Russell, Georg Lentzen, Jalal Haddad, Shahriar Mobashery

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The X-ray crystal structures for the complexes of three designer antibiotics, compounds 1, 2, and 3, bound to two models for the ribosomal aminoacyl-tRNA site (A site) at 2.5-3.0 Å resolution and that of neamine at 2.8 Å resolution are described. Furthermore, the complex of antibiotic 1 bound to the A site in the entire 30S ribosomal subunit of Thermus thermophilus is reported at 3.8 Å resolution. Molecular dynamics simulations revealed that the designer compounds provide additional stability to bases A1492 and A1493 in their extrahelical forms. Snapshots from the simulations were used for free energy calculations, which revealed that van der Waals and hydrophobic effects were the driving forces behind the binding of designer antibiotic 3 when compared to the parental neamine.

Original languageEnglish (US)
Pages (from-to)129-138
Number of pages10
JournalChemistry and Biology
Volume13
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

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Transfer RNA
Anti-Bacterial Agents
Thermus thermophilus
Ribosome Subunits
Molecular Dynamics Simulation
Free energy
Molecular dynamics
Crystal structure
X-Rays
X rays
Computer simulation
neamine

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Interactions of designer antibiotics and the bacterial ribosomal aminoacyl-tRNA site. / Murray, James B.; Meroueh, Samy; Russell, Rupert J M; Lentzen, Georg; Haddad, Jalal; Mobashery, Shahriar.

In: Chemistry and Biology, Vol. 13, No. 2, 02.2006, p. 129-138.

Research output: Contribution to journalArticle

Murray, James B. ; Meroueh, Samy ; Russell, Rupert J M ; Lentzen, Georg ; Haddad, Jalal ; Mobashery, Shahriar. / Interactions of designer antibiotics and the bacterial ribosomal aminoacyl-tRNA site. In: Chemistry and Biology. 2006 ; Vol. 13, No. 2. pp. 129-138.
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